Pancreatic secretory activity of secretin5-27 and substituted analogues.

The effect of secretin5-27 and four substituted analogues (9 Gln-secretin5-27, 15-Asn-secretin5-27, 9-Gln-15-Asn-secretin5-27, and 15-Lys-secretin5-27) on pancreatic secretion in the rat and guinea pig was examined. Secretin5-27 retained significant pancreatic secretory activity in both species. Its efficacy (intrinsic activity) relative to secretin was much higher in the rat (0.2) than in the guinea pig (0.03). The activity of secretin5-27 was not affected by a single or dual substitution of carboxylic acid residues by the corresponding carboxamides or by lysine despite a substantial decrease in the helical character of the peptide.

Mediation of guinea pig gastric secretion in vitro by cyclic nucleotides.

The effect of methacholine, theophylline, and cyclic adenyl and guanyl nucleotides on gastric secretion from antral and proximal duodenal mucosa of the guinea pig was studied. Both 2 mM dibutyryl (db) cAMP and 5 mM theophylline produced significant increases in gastrin secretion, 4.3 +/- 0.7 (P less than 0.001) and 9.3 +/- 2.4 pg mg-1 min-1 (P less than 0.005) respectively, above basal gastrin secretion (1.5 +/- 0.4 pg mg-1 min-1). The combined effect of the two agents was additive (14.5 +/- 3.6 pg mg-1 min-1). Db cGMP (2 mM) had no effect on gastrin secretion. Methacholine produced a dose-related increase in gastrin secretion which at maximum equaled the combined effect of theophylline and db cAMP. The results suggest that gastrin secretion is mediated in part by intracellular cAMP but do not exclude a cooperative involvement of cGMP.

Stimulation of insulin and glucagon secretion by vasoactive intestinal peptide.

In vivo, vasoactive intestinal peptide (VIP) produces simultaneous increases in blood glucose and insulin levels. In order to determine whether VIP, like its homologues, also stimulates insulin secretion directly, studies were made in controlled glucose media employing the vascularly perfused cat pancreas. VIP stimulated insulin secretion significantly in the presence of constant physiological concentrations of glucose. The highest insulin response to VIP (100.3+/-8.1 muU/min) approached the highest insulin response to glucose (119.9 +/- 12.0 muU/min). In the absence of glucose, the insulin response to VIP was insignificant. Unexpectedly, VIP was found to be a more effective stimulant of glucagon than of insulin secretion. The highest glucagon response to VIP (327+/-51% of control levels) was attained in the presence of physiological concentrations of glucose and equalled the glucagon response obtained upon withdrawal of glucose from the perfusate. The glucagon response to VIP was blocked by increasing the glucose in the perfusate. These studies indicate the VIP present in pancreatic islets might play a role in the local control of pancreatic endocrine function.

Clearance rate, half-life, and secretory potency of human gastrin-17-I in different species.

The clearance rates of synthetic human gastrin-17-I were measured in man, dog, and cat. Half-life of disappearance and acid secretory potency (D50) were also measured in man and dog. The clearance rates in dog and cat were, respectively, 3 and 8 times more than in man. Accordingly, the half-life of gastrin-17 in the dog (3.5 min) was 3 times shorter than in man (9.5 to 10.5 min). The D50 for acid secretion was proportional to the clearance rate and yielded approximately similar increments of serum gastrin, indicating an equal sensitivty to gastrin-17 at cellular level in the three species. An inverse allometric relation between clearance rate and body weight was consistent with the known greater efficiency of metabolic and eliminatory processes in species of small size. Recent studies of the disposal of other gastrointestinal hormones indicate that the concepts developed theoretically for secretory stimulants and confirmed experimentally for gastrin-17 may have wider applicability.